IPM is a rare neoplasm arising from the stromal component of the lymph node. Almost all cases develop in lymph nodes of the inguinal region. Although uncommon, it may also be seen in submandibular and mediastinal lymph nodes [7, 8]. Initially, it was defined as a malignant neurilemmoma, first by Deligdish et al in 1968 , and later by Katz et al in 1974 . In 1989, three groups of investigators described this tumor, giving it different names. Weis et al proposed the name "palisaded myofibroblastoma" , whereas Suster et al and Lee et al described it as "intranodal hemorrhagic spindle-cell tumor with amianthoid fibers" and "solitary spindle-cell tumor with myoid differentiation of the lymph node," respectively [2, 3]. Currently, the term "intranodal palisaded myofibroblastoma" is preferred because it reflects the myofibroblastic origin of the tumor, as well as its histomorphological composition of prominent palisaded spindle-cells, and its localization to lymph nodes.
IPM produces a slow-growing, painless inguinal mass. Numerous cases are seen among men between 45 and 55 years of age. Grossly, the section of the lymph node has a solid appearance and displays irregular hemorrhagic areas. Histopathologically, it is characterized by various microscopic properties. In most cases, the tumor is observed with lymphoid tissue compressed to the periphery of the lesion. Spindle cells with nuclear palisading, intraparenchymal hemorrhage and erythrocyte extravasation, collagen deposits called amianthoid fibers, and intracellular or extracellular bodies reacting with smooth-muscle actin (SMA) and vimentin, are all seen in these lesions. Immunohistochemically, the spindle cells are positive for SMA and vimentin. No reaction is observed with many other antibodies. The tumor cells exhibit a low proliferative index [1–3].
Weis proposed that IPM originated from the walls of blood vessels in the lymph node . The fact that inguinal lymph nodes have richer vascular components supports this claim. Moreover, immunohistochemical and electron microscopic findings have shown similarities between these lesions and the myofibroblasts and/or smooth muscle cells of blood vessels. Kleist et al demonstrated cyclin D1 expression in 50% of spindle cells in these lesions . Genetic studies conducted with the same cases did not show any mutations in the CCND1 gene locus. These investigators suggested that cyclin D1 over-expression develops independently from any genetic changes and influences the spindle cells as a growth factor . Genetic evidence associated with HHV-8 and Epstein - Barr virus (EBV) suggests that a viral mechanism of oncogenesis might be involved in the development of these lesions [5, 6].
Typically, IPM is composed of spindle cells. Therefore, pathologic differential diagnosis should comprise the large diagnostic spectrum in which spindle cells are involved. Malignant spindle-cell tumors and non-IPM benign mesenchymal lesions of the lymph node must be taken into account. To diagnose as IPM, non-IPM tumors or pseudotumors must be excluded clinically, histomorphologically, and immunohistochemically. Neoplasms that have spindle-cell morphology can originate from vascular endothelium, fibroblasts, histiocytes, smooth muscle cells, myofibroblasts, dendritic reticulum cells, or interdigitating reticulum cells, all of which are stromal components of lymph nodes. These rarely seen lesions can imitate IPM histologically.
Schwannoma and KS are the most important tumors in the differential diagnosis. Moreover, hemangioendothelioma, dendritic reticulum cell tumor, and inflammatory myofibroblastic tumor (IMT) should also be considered in the differential diagnosis [1–3, 11].
Schwannomas, extending through the peripheral nerve sheath, contain spindle cells with nuclear palisading and are often confused with IPM. Since it lacks peripheral nerve innervation, the lymph node is not expected to be a site of schwannoma development. Immunohistochemically, detection of S-100 immunoreaction contributes to the differential diagnosis of those two lesions.
Because IPM contains extravasated erythrocytes and hemosiderin pigments among the spindle cells, it may be mistaken for KS. In some IPM cases, detection of HHV-8 immunoreactivity reduces the utility of this marker in the differential diagnosis. However, histomorphologically, nuclear palisading and amianthoid fibers are not observed in KS. Moreover, the absence of immunoreaction with endothelial markers also supports an IPM diagnosis [12, 13].
IMT is characterized by proliferation of spindle cells in the lymph node, a vascular structure laid down by compressed endothelium, and a dense inflammatory cell component. That the amianthoid fibers observed in IPM are not present is very helpful for differential diagnosis, and an inflammatory component rich in plasma cells is included in these lesions, which otherwise have similar immunohistochemical profiles to IPM .
IPMs are well differentiated tumors with low proliferative activity. They have been agreed to have a benign biological behavior. For this reason, distinguishing them from primary and metastatic malignant lesions of the lymph node is important. Malignant spindle-cell tumors can infiltrate lymph nodes by direct invasion or by metastasis. Primary and metastatic sarcomas of lymph node can be recognized by their marked pleomorphism and atypia, high mitotic activity, and by the expression of features characteristic of the cells of origin.
Spindle-cell melanoma is another malignant tumor that must be taken into account in differential diagnosis. Hemosiderin pigment, which is frequently seen in IPM, can be confused with melanin histologically. It contributes to the differential diagnosis that in melanomas, S-100 and HMB-45 immunoreactivity are seen in spindle cells. Unlike IPM, carcinomas express epithelial indicators (i.e., keratin, EMA) show marked atypia and pleomorphism and have high proliferative activity [11–14].
Since IPM forms a mass in the inguinal region, cytological samples can be obtained. Martinez et al described the cytological characteristics of these lesions as spindle cells with no nuclear atypia on smears with moderate cellularity, fibrillar background material, and hemosiderin granules and hemosiderin-laden histiocytes . The biological behavior of these lesions is benign. In the literature, the local recurrence rate is about 6%, and no malignant transformation has been reported [1–3, 12–15]. Regarding treatment, total removal of the lesion suffices.
Our case was a male patient at an advanced age, presenting with an IPM in the inguinal region, the typical location for that tumor. This painless and slow-growing lesion was evaluated to be clinically consistent with lymphadenopathy, and was excised with the prediagnosis of lymphoma. Microscopic diagnostic features of IPM, such as spindle cells with nuclear palisading, amianthoid fibers, hemosiderin pigment, and extravasated erythrocytes, were observed in this case. Residual lymphoid tissue was found to be compressed to the periphery of the lesion. Histochemically, amianthoid fibers showed staining for collagen, whereas the spindle cells stained as muscle. Immunohistochemically, spindle cells displayed a positive reaction for SMA. Our findings support the suggestion that these tumors arise from differentiated smooth muscle or myofibroblastic cells. In our case, no immunoreaction with cyclin D1 or HHV-8 was observed.
In conclusion, IPM, a rare tumor, should be considered in differential diagnosis because of its ability to mimic metastatic lesions in the lymph node. Future studies supported by molecular techniques and performed on large tumor series should further explain the pathogenesis of those lesions.